ASCO 2013 – personalised medicine: potential and challenges

In our third instalment from the ASCO cancer conference, Debbie Coates writes about a major theme of modern cancer research – the concept of personalised medicine.

It’s an exciting time in the world of cancer treatment. We know more than ever before about the genetic faults driving different cancers, and we’re getting better at designing drugs that target them.

At the same time, it’s becoming clear that the more we know, the more complicated things become. As we start using genetics to classify tumours, we find that the number of cancer types is growing rapidly – for example, only last year our scientists in Cambridge showed that breast cancer is actually at least ten different diseases.

There are also huge challenges with developing drugs targeting these changes – not least designing the clinical trials to test them.

Several sessions at this year’s ASCO conference discussed the issues being thrown up by our progress into the era of personalised medicine.

A key problem is that the genes faults differ from one cancer type to another – the ones we commonly see in breast cancer aren’t always the ones we see in lung or bowel cancer, for example. And when we do occasionally see faults that are common in many different cancers, we don’t yet have the drugs to target them.

Another problem is that, in a single type of cancer, there may be a very small numbers of patients with a particular mutation. This means researchers will need to adapt the way they design trials to show whether a drug works for people who have that particular mutation.

We also have to face up to the idea that different groups of cells within a tumour have different genetic faults – an issue known as ‘intratumour heterogeneity’. This suggests that doctors will need to figure out what’s going on in different parts of the tumour (for example by taking multiple biopsies, or working out how to analyse DNA in the bloodstream).

And it also implies that not all cells within a cancer can be targeted by a single drug. So using combinations of targeted drugs – or using them in particular sequences – may be needed.

The repertoire of gene faults within a tumour may also change over time, so several speakers suggested that doctors cannot just rely on initial biopsies when planning treatments – they’ll probably need to keep monitoring things over time to find out whether the genetic make-up has changed.

But some of the gene changes may make the cancer resistant to particular drugs, and treatments themselves can sometimes cause genetic changes. We’re learning more and more about this and our very own Professor Charles Swanton gave an excellent talk about the research his team is doing into this important area.

With so many different genetic changes and emerging targeted treatments, it can be difficult for doctors to match their patient to the drug most likely to work for them. In response to this, ASCO has developed a data bank called CancerLINQ, which is collecting data about patients, treatments and the effectiveness of treatments.

Doctors can share their data and so speed up the rate at which we can identify the most effective targeted treatments and find out the best ways of using them.

Finally, Dr David Solit of the Memorial Sloan Kettering Cancer Centre, New York talked about his work looking at secondary tumours (aka tumour spread or metastases). He highlighted that secondary tumours can differ from each other as well as from the primary tumour – and that tumour heterogeneity can also exist in a secondary tumour.

This helps us understand why some areas of metastasis may shrink in response to a particular treatment but other areas of metastasis may continue to grow. This again has implications for future treatment.

Dr Solit also described how cells from a secondary tumour can break away, circulate in the blood and reach the primary tumour – delivering cells with new genetic changes – a phenomenon he referred to as ‘self-seeding of the primary’. All in all, keeping up with how primary and secondary tumours change over time will pose quite a challenge.

It would be easy to feel disheartened by all these challenges. But in between and after presentations, you can see scientists and doctors gathering to debate, brainstorm and forge new collaborations – energised and undaunted by the sheer scale of the task they face. The clear message from this year’s ASCO is that we are up for the fight.

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